Disease relevance of JTE-522

• Our data also indicate that JTE-522 is a potent chemopreventive agent of rat liver fibrosis with low toxicity [1].
• JTE-522 administrated only from 12 weeks to 36 weeks also prevented cirrhosis and formation of hepatocellular carcinoma [1].
• Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents [2].
• We investigated the effect of 0, 10 and 30 mg/kg/day of JTE-522 on the angiogenesis of pulmonary metastases in 3 groups of 5 male rats out of 25 [3].
• These findings suggest that JTE-522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon [4].

Psychiatry related information on JTE-522

• Starting at 4 weeks of age, the treated group (T group) were given a diet containing JTE-522, a selective COX-2 inhibitor, and the control group (C group) were given a control diet [5].

High impact information on JTE-522

• JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1 [1].
• JTE-522 significantly inhibited fibrosis and development of preneoplastic lesions in a dose-dependent manner and completely inhibited generation of cirrhosis and hepatocellular carcinoma at both low and high doses (10 and 30 mg/kg body wt/day, respectively) [1].
• METHODS: We investigated the inhibitory effects of a selective COX-2 inhibitor, JTE-522, on liver fibrosis induced by a choline-deficient, l-amino acid-defined diet (CDAA) [1].
• In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro [6].
• Addition of a selective COX-2 inhibitor, JTE-522, to cocultures of mammary carcinoma cell lines and bone marrow cells lowered PGE2 concentration in the culture media and inhibited osteoclast formation in a dose-dependent manner [7].

Chemical compound and disease context of JTE-522

• RESULTS: JTE-522 inhibited the development of carrageenin-induced paw edema and PGE2 production in inflammatory paws at a dose of 10 mg/kg [8].
• Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo [9].
• This hyperalgesia could be reversed by pretreatment of the rats with indomethacin, a cyclooxygenase-2-selective inhibitor JTE-522 (10 mg/kg, p.o.), or FR173657, but not with mofezolac [10].

Biological context of JTE-522

• A COX-2 inhibitor, JTE-522, inhibited cell proliferation and invasion of LM-H3 in vitro and clearly reduced the number of metastatic nodules on the surface of nude mouse livers in vivo [11].
• Furthermore, microarray analyses revealed that JTE-522 had no effect on gene expression levels in DMH-induced tubular adenocarcinomas [4].
• The synergy achieved in cytotoxicity with JTE-522 and 5-FU was shown to be due to apoptosis [12].
• JTE-522, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide , is a selective inhibitor of cyclooxygenase-2 at the enzyme level (IC50 is 6.4 x 10(-7) M for sheep cyclooxygenase-2, but it does not inhibit sheep cyclooxygenase-1 at concentrations up to 10(-4) M) [13].
• The effect of food-intake on the pharmacokinetics of JTE-522 at a dose of 150 mg was examined [14].

Anatomical context of JTE-522

• Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used [15].
• JTE-522 at the concentrations of 10(-5) and 10(-6) M significantly decreased the growth-stimulating activity of gastric fibroblasts [15].
• JTE-522 inhibited the VEGF expression of these macrophages, resulting in a decrease in vascular area [5].
• These findings suggest that JTE-522 has a high affinity for blood cells and the distribution into blood cells is limited at the higher doses of over 100 mg [14].
• AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim) [16].

Associations of JTE-522 with other chemical compounds

• RESULTS: Combination treatment of T24 bladder cancer cells with JTE-522 and cis-diamminedichloroplatinum (II) (CDDP) resulted in a synergistic cytotoxic effect [17].
• Spontaneously breathing guinea pigs were exposed to ozone (3 ppm) for 2 h after treatment with vehicle, indomethacin (10 mg/kg) or JTE-522 (10 mg/kg) [18].
• In a cell-based assay, JTE-522 diminished lipopolysaccharide-induced prostaglandin E2 production in human peripheral blood mononuclear cells (COX-2) (IC50 value = 15.1 nM) [19].
• RESULTS: JTE-522 (from 0.3 mg/kg) suppressed the development of paw swelling, and also reduced bone damage (score and bone mineral density) in arthritic paws and the urinary excretion of deoxypyridinoline and pyridinium crosslinks [20].
• On the other hand, JTE-522 (1-100 mg/kg) did not affect A23187-stimulated thromboxane B2 release from whole blood or the PGE2 level in gastric mucosa [8].

Gene context of JTE-522

• These data indicate that the COX-2 inhibitor JTE-522 has a high potential for use as a clinical agent for the treatment of liver metastasis of colon cancer [11].
• JTE-522 downregulated PDGF production by LM-H3 but had no influence on VEGF production [11].
• JTE-522 also inhibited MMP-2 secretion by LM-H3 [11].
• Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522 [21].
• In contrast, the inhibitory activity of JTE-522 on human COX-1 was not affected by preincubation time [19].

Analytical, diagnostic and therapeutic context of JTE-522

• Furthermore, the adjunct use of JTE-522 is shown to significantly enhance treatment efficacy of conventional anticancer drugs not only in vitro but also in vivo without causing any noticeable side effects [2].
• We also examined the effects of JTE-522 on the production of growth factors and MMPs through the use of ELISA and gelatin zymography, respectively [11].
• The diameter of tumor vessels and the size of lung metastases significantly and positively correlated with neovascularization in the control group, but not in the JTE-522-treated groups [3].
• Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR [15].
• Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice [15].

References